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https://www.readbyqxmd.com/read/28641935/fatty-acid-modified-gapmer-antisense-oligonucleotide-and-serum-albumin-constructs-for-pharmacokinetic-modulation
#1
Michael Lykke Hvam, Yunpeng Cai, Frederik Dagnæs-Hansen, Jesper Sejrup Nielsen, Jesper Wengel, Jørgen Kjems, Kenneth A Howard
Delivery technologies are required for realizing the clinical potential of molecular medicines. This work presents an alternative technology to preformulated delivery systems by harnessing the natural transport properties of serum albumin using endogenous binding of gapmer antisense oligonucleotides (ASOs)/albumin constructs. We show by an electrophoretic mobility assay that fatty acid-modified gapmer and human serum albumin (HSA) can self-assemble into constructs that offer favorable pharmacokinetics. The interaction was dependent on fatty acid type (either palmitic or myristic acid), number, and position within the gapmer ASO sequence, as well as phosphorothioate (PS) backbone modifications...
June 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28641556/pharmacogenetic-and-pharmacokinetic-dose-individualization-of-the-taxane-chemotherapeutic-drugs-paclitaxel-and-docetaxel
#2
Natália Bordin Andriguetti, Suziane Raymundo, Marina Venzon Antunes, Magda Susana Perasolo, Simone Gasparin Verza, Edna Sayuri Suyenaga, Rafael Linden
The taxane drugs paclitaxel and docetaxel, widely used on cancer chemotherapy, are currently dosed mainly based on body-surface area. This approach is associated with wide interindividual variability in drug exposure, leading to suboptimal dosing for many patients. We reviewed the available evidence supporting dose individualization strategies for paclitaxel and docetaxel, focusing mainly on the application of therapeutic drug monitoring by a priori pharmacogenetic data or a posteriori drug measurements in biological fluids...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28641538/glt-1-upregulation-as-a-potential-therapeutic-target-for-ischemic-brain-injury
#3
Yu-Yan Hu, Li Li, Xiao-Hui Xian, Min Zhang, Xiao-Cai Sun, Shu-Qin Li, Xin Cui, Jie Qi, Wen-Bin Li
Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, which plays an important role in many aspects of normal brain function such as neural development, motor functions, learning and memory etc. However, excessive accumulation of glutamate in the extracellular fluid will induce excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia. There is no enzyme to decompose the glutamate in extracellular fluid, so extracellular glutamate homeostasis within the central nervous system is mainly regulated by the uptake activity of excitatory amino acid transporters...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28639394/transferrin-conjugated-magnetic-dextran-spermine-nanoparticles-for-targeted-drug-transport-across-blood-brain-barrier
#4
Maryam Ghadiri, Ebrahim Vasheghani-Farahani, Fatemeh Atyabi, Farzad Kobarfard, Farzaneh Mohamadyar-Toupkanlou, Hossein Hosseinkhani
Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28638781/bioinspired-mechano-sensitive-macroporous-ceramic-sponge-for-logical-drug-and-cell-delivery
#5
Changlu Xu, Zhihao Wei, Huajian Gao, Yanjie Bai, Huiling Liu, Huilin Yang, Yuekun Lai, Lei Yang
On-demand, ultrahigh precision delivery of molecules and cells assisted by scaffold is a pivotal theme in the field of controlled release, but it remains extremely challenging for ceramic-based macroporous scaffolds that are prevalently used in regenerative medicine. Sea sponges (Phylum Porifera), whose bodies possess hierarchical pores or channels and organic/inorganic composite structures, can delicately control water intake/circulation and therefore achieve high precision mass transportation of food, oxygen, and wastes...
June 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28636761/molecular-tools-for-facilitative-carbohydrate-transporters
#6
Marina Tanasova, Joseph R Fedie
Facilitative carbohydrate transporters - Gluts - have received a wide attention over decades due to their essential role in the nutrient uptake and links with various metabolic disorders, including diabetes, obesity, and cancer. Endeavors into understanding mechanisms of Glut-mediated nutrient uptake have resulted in the multidisciplinary research field, branching protein chemistry, chemical biology, organic synthesis, crystallography, and biomolecular modeling. Gluts became attractive targets for cancer research and medicinal chemistry, leading to the development of new approaches to cancer diagnostics and providing avenues for cancer-targeting therapeutics...
June 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28630154/design-of-self-assembling-transmembrane-helical-bundles-to-elucidate-principles-required-for-membrane-protein-folding-and-ion-transport
#7
REVIEW
Nathan H Joh, Gevorg Grigoryan, Yibing Wu, William F DeGrado
Ion transporters and channels are able to identify and act on specific substrates among myriads of ions and molecules critical to cellular processes, such as homeostasis, cell signalling, nutrient influx and drug efflux. Recently, we designed Rocker, a minimalist model for Zn(2+)/H(+) co-transport. The success of this effort suggests that de novo membrane protein design has now come of age so as to serve a key approach towards probing the determinants of membrane protein folding, assembly and function. Here, we review general principles that can be used to design membrane proteins, with particular reference to helical assemblies with transport function...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28627473/glycyrrhetic-acid-but-not-glycyrrhizic-acid-strengthened-entecavir-activity-by-promoting-its-subcellular-distribution-in-the-liver-via-efflux-inhibition
#8
Qianying Chen, Hongzhu Chen, Wenjie Wang, Jiali Liu, Wenyue Liu, Ping Ni, Guowei Sang, Guangji Wang, Fang Zhou, Jingwei Zhang
Entecavir (ETV) is a superior nucleoside analogue used to treat hepatitis B virus (HBV) infection. Although its advantages over other agents include low viral resistance and the elicitation of a sharp decrease in HBV DNA, adverse effects such as hepatic steatosis, hepatic damage and lactic acidosis have also been reported. Glycyrrhizin has long been used as hepato-protective medicine. The clinical combination of ETV plus glycyrrhizin in China displays better therapeutic effects and lower rates of liver damage...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#9
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28627037/quantitative-gd-dota-uptake-from-cerebrospinal-fluid-into-rat-brain-using-3d-vfa-spgr-at-9-4t
#10
Hedok Lee, Kristian Mortensen, Simon Sanggaard, Palle Koch, Hans Brunner, Bjørn Quistorff, Maiken Nedergaard, Helene Benveniste
PURPOSE: We propose a quantitative technique to assess solute uptake into the brain parenchyma based on dynamic contrast-enhanced MRI (DCE-MRI). With this approach, a small molecular weight paramagnetic contrast agent (Gd-DOTA) is infused in the cerebral spinal fluid (CSF) and whole brain gadolinium concentration maps are derived. METHODS: We implemented a 3D variable flip angle spoiled gradient echo (VFA-SPGR) longitudinal relaxation time (T1) technique, the accuracy of which was cross-validated by way of inversion recovery rapid acquisition with relaxation enhancement (IR-RARE) using phantoms...
June 19, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28626426/potential-of-central-eastern-and-western-africa-medicinal-plants-for-cancer-therapy-spotlight-on-resistant-cells-and-molecular-targets
#11
REVIEW
Armelle T Mbaveng, Victor Kuete, Thomas Efferth
Cancer remains a major health hurdle worldwide and has moved from the third leading cause of death in the year 1990 to second place after cardiovascular disease since 2013. Chemotherapy is one of the most widely used treatment modes; however, its efficiency is limited due to the resistance of cancer cells to cytotoxic agents. The present overview deals with the potential of the flora of Central, Eastern and Western African (CEWA) regions as resource for anticancer drug discovery. It also reviews the molecular targets of phytochemicals of these plants such as ABC transporters, namely P-glycoprotein (P-gp), multi drug-resistance-related proteins (MRPs), breast cancer resistance protein (BCRP, ABCG2) as well as the epidermal growth factor receptor (EGFR/ErbB-1/HER1), human tumor suppressor protein p53, caspases, mitochondria, angiogenesis, and components of MAP kinase signaling pathways...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28624793/bufalin-reverses-abcb1-mediated-drug-resistance-in-colorectal-cancer
#12
Ze-Ting Yuan, Xiao-Jing Shi, Yu-Xia Yuan, Yan-Yan Qiu, Yu Zou, Cheng Liu, Hui Yu, Xue He, Ke Xu, Pei-Hao Yin
Multidrug resistance (MDR), mainly mediated by ABCB1 transporter, is a major cause for chemotherapy failure. Bufalin (BU), an active component of the traditional Chinese medicine chan'su, has been reported to have antitumor effects on various types of cancer cells. The purpose of this present study was to investigate the reversal effect of BU on ABCB1-mediated multidrug resistance in colorectal cancer. BU at safe concentration (5, 10, 20 nM) could reverse chemosensitivity of ABCB1-overexpression HCT8/ADR, LoVo/ADR and HCT8/ABCB1 nearly back to their parental cells level...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623927/caffeoylquinic-acid-derivatives-rich-extract-from-gnaphalium-pensylvanicum-willd-ameliorates-hyperuricemia-and-acute-gouty-arthritis-in-animal-model
#13
Yan Jiang, Yan Lin, Yi-Juan Hu, Xiao-Jun Song, Hong-Hua Pan, Hong-Jian Zhang
BACKGROUND: The Gnaphalium pensylvanicum willd. is used in China as a folk medicine to treat anti-inflammatory, cough and rheumatism arthritis. The aim of this study was to evaluate the potential of the extract of G. pensylvanicum to treat hyperuricemia and acute gouty arthritis in animal model. METHODS: G. pensylvanicum extract was evaluated in an experimental model with potassium oxonate (PO) induced hyperuricemia in mice which was used to evaluate anti-hyperuricemia activity and xanthine oxidase (XO) inhibition...
June 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28621878/isolation-and-chemical-characterization-of-agelaiatoxin8-avtx8-from-agelaia-vicina-wasp-venom-and-its-biological-effects-on-gaba-neurotransmission
#14
Andrea B Pizzo, Renê O Beleboni, Ruither O Gomes Carolino, Luciana de Oliveira, Antonio Miranda, Joaquim Coutinho-Netto, Andréia C K Fontana, Wagner Ferreira Dos Santos
Arthropod venoms are sources of molecules that may be useful tools to investigate molecular mechanisms of putative new medicines and laboratory drugs. Here we show the effects of the compound agelaiatoxin-8 (AVTx8), isolated from Agelaia vicina venom, on γ-aminobutyric acid (GABA) neurotransmission in rat brain synaptosomes. Analysis reveals that AvTx8 is composed by 14 amino acid residues with a molecular weight (MW) of 1567 Da. AvTx8 increased GABA release and inhibited GABA uptake in synaptosomes from rat cerebral cortex...
June 16, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28619110/effect-of-aspartic-acid-and-glutamate-on-metabolism-and-acid-stress-resistance-of-acetobacter-pasteurianus
#15
Haisong Yin, Renkuan Zhang, Menglei Xia, Xiaolei Bai, Jun Mou, Yu Zheng, Min Wang
BACKGROUND: Acetic acid bacteria (AAB) are widely applied in food, bioengineering and medicine fields. However, the acid stress at low pH conditions limits acetic acid fermentation efficiency and high concentration of vinegar production with AAB. Therefore, how to enhance resistance ability of the AAB remains as the major challenge. Amino acids play an important role in cell growth and cell survival under severe environment. However, until now the effects of amino acids on acetic fermentation and acid stress resistance of AAB have not been fully studied...
June 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28615044/comparison-of-transportation-related-injury-mechanisms-and-outcome-of-young-road-users-and-adult-road-users-a-retrospective-analysis-on-24-373-patients-derived-from-the-traumaregister-dgu-%C3%A2
#16
Thomas Brockamp, Uli Schmucker, Rolf Lefering, Manuel Mutschler, Arne Driessen, Christian Probst, Bertil Bouillon, Paola Koenen
BACKGROUND: Most young people killed in road crashes are known as vulnerable road users. A combination of physical and developmental immaturity as well as inexperience increases the risk of road traffic accidents with a high injury severity rate. Understanding injury mechanism and pattern in a group of young road users may reduce morbidity and mortality. This study analyzes injury patterns and outcomes of young road users compared to adult road users. The comparison takes into account different transportation related injury mechanisms...
June 14, 2017: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/28612105/-polytrauma-and-concomitant-traumatic-brain-injury-the-role-of-the-trauma-surgeon
#17
REVIEW
A Antoni, T Heinz, J Leitgeb
BACKGROUND: Concomitant traumatic brain injury (TBI) increases mortality and reduces quality of life of polytrauma patients. These facts demand effective treatment strategies while the growing specialization of medicine is questioning the role of the trauma surgeon in the management of these patients. OBJECTIVES: Which factors influence outcome of polytrauma with concomitant TBI? Who should be responsible for the management of these patients and what is the limit of management? MATERIALS AND METHODS: A literature search using Medline via PubMed was performed with Medical Subject Headings and text word search...
June 13, 2017: Der Unfallchirurg
https://www.readbyqxmd.com/read/28610596/complete-human-serum-maintains-viability-and-chondrogenic-potential-of-human-synovial-stem-cells-suitable-conditions-for-transplantation
#18
Mitsuru Mizuno, Hisako Katano, Koji Otabe, Keiichiro Komori, Yuji Kohno, Shizuka Fujii, Nobutake Ozeki, Masafumi Horie, Kunikazu Tsuji, Hideyuki Koga, Takeshi Muneta, Ichiro Sekiya
BACKGROUND: In our clinical practice, we perform transplantations of autologous synovial mesenchymal stem cells (MSCs) for cartilage and meniscus regenerative medicine. One of the most important issues to ensuring clinical efficacy involves the transport of synovial MSCs from the processing facility to the clinic. Complete human serum (100% human serum) is an attractive candidate material in which to suspend synovial MSCs for their preservation during transport. The purpose of this study was to investigate whether complete human serum maintained MSC viability and chondrogenic potential and to examine the optimal temperature conditions for the preservation of human synovial MSCs...
June 13, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28608962/image-based-computational-fluid-dynamics-in-the-lung-virtual-reality-or-new-clinical-practice
#19
REVIEW
Kelly S Burrowes, Jan De Backer, Haribalan Kumar
The development and implementation of personalized medicine is paramount to improving the efficiency and efficacy of patient care. In the respiratory system, function is largely dictated by the choreographed movement of air and blood to the gas exchange surface. The passage of air begins in the upper airways, either via the mouth or nose, and terminates at the alveolar interface, while blood flows from the heart to the alveoli and back again. Computational fluid dynamics (CFD) is a well-established tool for predicting fluid flows and pressure distributions within complex systems...
June 13, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28608578/cantharidin-inhibits-competitively-heme-fe-iii-binding-to-the-fa1-site-of-human-serum-albumin
#20
Fabio Polticelli, Loris Leboffe, Valentina Tortosa, Viviana Trezza, Gabriella Fanali, Mauro Fasano, Paolo Ascenzi
Cantharidin, a monoterpene isolated from the insect blister beetle, has long been used as a medicinal agent in the traditional Chinese medicine. Cantharidin inhibits a subgroup of serine/threonine phosphatases, thus inducing cell growth inhibition and cytotoxicity. Cantharidin has anticancer activity in vitro, since it is able of inducing p53-dependent apoptosis and double-strand breakage of DNA in cancer cells. Although the toxicity of cantharidin to the gastrointestinal and urinary tracts prevents its medical use, it is a promising lead compound for chemical modification to develop new anticancer therapeutics...
June 13, 2017: Journal of Molecular Recognition: JMR
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